This proposal describes a development award for Dr. Secor, a Naturopathic Physician and Licensed Acupuncturist, to successfully achieve his long term career goals of becoming an independent investigator focused on the immunomodulatory effects of natural products through translational research. This proposal combines advanced academics, research training, outstanding mentorship and consultation to promote professional career development. Dr. Secor has successfully completed a NIH/NCCAM F32 Post Doctoral Fellowship at the University of Connecticut Health Center in the Department of Immunology. His research has demonstrated that Bromelain (Br), a pineapple extract, exerted anti-inflammatory and immunomodulatory effects in an ovalbumin (OVA)-induced mouse model of allergic airway disease (AAD) via reduced CD4+ T cells, eosinophils, and Th2 cytokines. We have observed that Br treatment reduces CD25, a key activation marker on CD4+ T cells as well as alters MHC-II and CD86 levels on antigen presenting cells (APCs), such as Dendritic Cells (DCs) and B cells. We hypothesize that the therapeutic benefits of Br in this OVA-induced model occur via immunomodulatory effects on CD4+ T cells specifically by: 1) Direct inhibition of CD4+ T cell activation via IL-2 signaling, 2) Direct inhibition of antigen presenting cells (DCs and B cells). Specific Aim 1 will determine the in vivo effects of Br treatment on CD4+ T cells and APCs in local compartments (BAL, lung tissue, hilar lymph nodes) and systemic compartments (inguinal lymph nodes, spleen) at each of the 4 stages of the OVA model: Sensitization, AAD, Continuous LIT and Discontinuous AAD. Specific Aim 2 will determine the specific mechanism(s) of action of Br by in vitro treatment of CD4+ T cells, DCs and B cells isolated from local and systemic compartments during the 4 stages of the OVA model. Botanicals with unknown mechanisms of action are widely used by the general public in the treatment and management of acute and chronic conditions such as allergy and asthma. The effect of botanicals and their extracts on the immune system is an exciting new area of research. These studies will help elucidate the anti-inflammatory mechanism(s) of action of Br and provide rigorous advanced training to a CAM clinician, all of which are directly relevant to the mission of NCCAM.